Up-regulation of Akt and eNOS induces vascular smooth muscle cell differentiation in hypertension in vivo

Recent studies have shown that angiotensin II type 1 (AT1) receptor-mediated Akt activation induces vascular smooth muscle cell (VSMC) dedifferentiation in vitro. However, the critical signal transductions affecting the VSMC phenotype remain unclear in vivo. We examined whether signal transduction through AT1 receptor-mediated reactive oxygen species (ROS) could regulate the VSMC phenotype in stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were randomized and treated for 6 weeks with a vehicle, an ACE inhibitor cilazapril, or an AT1 receptor antagonist E4177. The 2 drugs showed equipotent effects on the blood pressure, aortic morphology, and collagen deposition. Both drugs also significantly reduced aortic NAD(P)H oxidase activity and p38MAPK and ERK expression, whereas p-Akt, eNOS, and SM2 were significantly increased in SHRSP aortas. Furthermore, E4177 was more effective than cilazapril at inducing VSMC differentiation by reducing NAD(P)H oxidase activity, and up-regulating p-Akt, eNOS, and SM2. Thus, an ACE inhibitor and an AT1 receptor antagonist inhibited VSMC dedifferentiation through inhibition of NAD(P)H oxidase activity and up-regulation of eNOS and Akt in SHRSP aortas, suggesting that in contrast to the in vitro experiments, AT1 receptor-mediated NAD(P)H oxidase-generated ROS, eNOS, and Akt might be crucial determinants for the VSMC phenotype in hypertension in vivo.     

Hepatoma-derived growth factor as a prognostic marker in completely resected non-small-cell lung cancer

Hepatoma-derived growth factor (HDGF), unrelated to hepatocyte growth factor, is a heparin-binding protein originally purified from human hepatoma HuH-7 cells. HDGF exhibits mitogenic activities for certain hepatoma cells, fibroblasts and vascular smooth muscle cells, and angiogenic activities through nuclear targeting. Recently, HDGF was found to be a mitogen for lung epithelial cells in vitro and in vivo. This suggests that HDGF may play a critical role in the development and progression of lung cancer. We investigated, immunohistochemically, the relationship between HDGF expression and clinicopathological variables, and the prognostic significance of HDGF in 102 patients with completely resected non-small-cell lung cancer (NSCLC: 70 adenocarcinomas and 32 squamous cell carcinomas). To address the mechanism of action of HDGF, we evaluated the contribution of HDGF to tumor cell proliferation and intratumor angiogenesis using anti-Ki-67 and anti-CD31 antibodies, respectively. HDGF expression was strongly detected in the nucleus of cancer cells; the HDGF-labeling index (LI) was 20-95% (median 64.5%). There was no significant association between HDGF-expression level and clinicopathological variables. Patients with NSCLC showing a high HDGF-LI (> or =65%) had significantly worse overall and disease-free survivals than those with NSCLC showing a low HDGF-LI. Multivariate analysis revealed that HDGF is a significant independent prognostic factor, more powerful than pathological stage. Moreover, HDGF expression correlated with Ki-67-LI and intratumor microvessel density. We consider HDGF as a useful prognostic marker for patients with completely resected NSCLC and it may play a critical role in the pathobiology of lung cancer through its mitogenic and angiogenic activities.     

Biological evaluation on glass ionomer cement.

Biological properties of a new dental cement of glass ionomer cement were compared with other types of conventional cement. The biological test was carried out by tissue culture method and animal examination. The culture cells showed weaker reaction to the glass ionomer cement than zinc oxide-eugenol or polycarboxylate cement. Pulp tissue reaction showed no significant difference between glass ionomer and zinc oxide-eugenol cement from in vivo experiments using monkeys.     

Stercoraceous perforation of the sigmoid colon: Report of two cases

Stercoraceous perforation of the sigmoid colon has rarely been reported in the literature. This lesion is assumed to be produced by the pressure from a hard scybalum resulting in a perforated ulcer with necrotic edges. Two cases of stercoraceous perforation of the sigmoid colon are presented in this paper. It is difficult to diagnose this lesion preoperatively, although ultrasonograms proved useful in showing the colon perforation. This lesion should always be suspected when a patient who has had chronic constipation presents with sudden severe abdominal pain. It is possible that this lesion is becoming more common as the mean age of the population increases and we stress the importance of immediate surgery and intensive care for improving the prognosis.     

Very Late Stent Thrombosis after Discontinuation of Antiplatelet Agents during Anticoagulation Therapy in a Patient with Peri-stent Contrast Staining after Implantation of a Second-generation Drug-eluting Stent

A 54-year-old man was admitted to our hospital due to intermittent chest pain. He had a history of acute myocardial infarction, and peri-stent contrast staining had been observed at the stent implantation site. The patient previously underwent anticoagulation therapy for left ventricular thrombus and antiplatelet therapy to prevent stent thrombosis. More than one year after implantation of a drug-eluting stent, antiplatelet drugs were discontinued, and anticoagulant alone was prescribed according to the guidelines, which resulted in very late stent thrombosis. The risks of both bleeding and thrombosis must be fully considered when deciding whether or not to discontinue antiplatelet therapy during anticoagulation therapy.     

In vitro activities of newly developed quinolones, fleroxacin, lomefloxacin and sparfloxacin against Mycobacterium tuberculosis

In vitro antituberculous activities of three newly developed quinolones, fleroxacin (FLRX, AM-833), lomefloxacin (LFLX) and sparfloxacin (SPFX, AT-4140) were evaluated in comparison to that of ofloxacin (OFLX) using M. tuberculosis strains isolated from patients and the Ogawa egg medium. SPFX was apparently more active than OFLX, but both FLRX and LFLX were less active. SPFX inhibited completely the growth of all 20 strains of M. tuberculosis isolated from patients who were not previously treated with OFLX in a concentration of 1.25 micrograms/ml. However, this agent inhibited the growth of only 4 strains (28.6%) of 14 OFLX-resistant M. tuberculosis in a concentration of 1.25 micrograms/ml, suggesting a partial cross-resistance between SPFX and OFLX.     

Endoscopic submucosal dissection for cancers of the remnant stomach after distal gastrectomy

BACKGROUND: Endoscopic submucosal dissection (ESD) of early gastric cancer is less invasive than surgical resection, and if technically feasible, it may result in less long-term morbidity than does incisional surgery. However, ESD is technically difficult in patients who have had a previous distal gastrectomy. OBJECTIVE: Our purpose was to retrospectively assess the results of ESD of early gastric cancer in the remnant stomach. DESIGN: Case series. SETTING AND PATIENTS: A total of 31 lesions in 30 patients with early remnant gastric cancer were treated with ESD at Okayama University Hospital, Tsuyama Central Hospital, Hiroshima City Hospital, Kagawa Prefectural Central Hospital, and Mitoyo General Hospital from March 2001 to January 2007. INTERVENTION: ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, complete resection rate, operation time, and complications. RESULTS: En bloc resection and complete resection were achieved in 30 (97%) and in 23 (74%) lesions, respectively. The median operation time required for ESD in the remnant stomach was 113 minutes (range 45-450 minutes). Perforation occurred in 4 (13%). The incidence of delayed bleeding requiring blood transfusion was 0%. LIMITATION: Short duration of follow-up. CONCLUSIONS: ESD is feasible in the remnant stomach but has a relatively high complication rate and should only be performed by experienced endoscopists.     

Benign biliary stricture associated with atherosclerosis

We report a case of benign bile duct stricture that could not be differentiated from intrahepatic bile duct carcinoma preoperatively. The patient was a 79-year-old man. Computed tomography showed dilatation of the intrahepatic bile duct in the left lobe. Direct cholangiography showed segmental stricture of the left bile duct. Angiography showed narrowing of the left hepatic artery. Although bile cytology did not show malignant cells, we suspected intrahepatic bile duct carcinoma preoperatively. We performed extended left hepatic lobectomy. Histopathologic examination of the resected duct also showed no malignant cells; fibrosis with infiltration by lymphocytes was seen at the bile duct stricture. In addition, the resected liver specimen showed sclerotic change in the intrahepatic arteries. The postoperative course was uneventful for more than 26 months, without recurrence or cholangitis. We encountered a very rare case of benign segmental bile duct stricture, which was difficult to differentiate from bile duct carcinoma. We think the biliary stricture was secondary to atherosclerosis which may have caused bile duct ischemia.     

Treatment of pyoderma gangrenosum with granulocyte and monocyte adsorption apheresis

Pyoderma gangrenosum is an intractable skin disorder characterized by the development of erythematous pustules or nodules that rapidly progress to destructive, necrotizing, non-infective ulcers. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy in two new patients, a 67-year-old man with ulcerations on his lower leg, and a 44-year-old man with turgid erythematous lesions with burrowing abscesses and sinus formation on his hip, groin, and thighs. Both patients received 10 GCAP treatments at 5-day intervals. Their skin lesions responded well. The 9 cmx6 cm ulcer on the lower right leg of the 67-year-old patient was completely covered by regenerated skin at the completion of therapy. The turgid skin lesions containing pustules and ulcers of the other patient showed amelioration and a marked decrease in the volume of exudate. Our results suggest that GCAP is a useful treatment modality for pyoderma gangrenosum.     

Transbronchial Cryobiopsy for Miliary Tuberculosis Mimicking Hypersensitivity Pneumonitis

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.